Caffeic Acid Phenethyl Ester (Phenylethyl Caffeate) (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways, with antineoplastic, cytoprotective and immunomodulating activities. CAPE is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).

Caffeic Acid Phenethyl Ester通过阻止NF-κB的p65亚单位进入核内，抑制了由棕榈酸酯、神经酰胺、骨脂酸和过氧化氢诱导的NF-κB激活。[1] 在多个肿瘤细胞系中，Caffeic Acid Phenethyl Ester展现出有希望的抗增殖活性，其EC50分别针对小鼠结肠26-L5细胞系、小鼠B16-BL6黑色素瘤细胞系、人类HT-1080纤维肉瘤细胞系和人类肺A549腺癌细胞系为1.76、3.16、13.7和44.0μM。[2] 作为一种强大的抗氧化剂，Caffeic Acid Phenethyl Ester在小脑颗粒细胞中发挥抗凋亡作用，其机制是通过阻断ROS形成和抑制caspase活性。[3] 此外，Caffeic Acid Phenethyl Ester减轻了LPS刺激的HSCs的促炎表型，并通过抑制NF-κB信号传导，减弱了LPS对HSCs诱导的对纤维生成细胞因子的敏感性。[4]

在体内，Caffeic Acid Phenethyl Ester（10 mg/kg，i.p.）抑制了接种Lewis肺癌、结肠癌和黑色素瘤细胞的C57BL/6和BALB/c小鼠原发性肿瘤的生长和血管生成。[5] Caffeic Acid Phenethyl Ester（5, 10, 20 mg/kg）通过减少胸腺重量和/或胸腺及脾脏的细胞性，还显示了体内的免疫调节效应。[6]

Human HT-1080 fibrosarcoma, human lung A549 adenocarcinoma and murine B16-BL6 melanoma cell lines are maintained in EMEM medium supplemented with 10% FCS, 0.1% sodium bicarbonate and 2 mM glutamine. Murine colon 26-L5 carcinoma cell line, on the other hand, is maintained in RPMI medium containing the same supplements as in EMEM. These are all highly metastatic cell lines except for A-549 carcinoma. Cellular viability is determined using the standard MTT assay. In brief, exponentially growing cells are harvested and 100 μl of cell suspension containing 2000 cells is plated in 96-well microtiter plates. After 24 h of incubation to allow for cell attachment, the cells are treated with varying concentrations of test samples in medium (100 μl) and incubated for 72 h at 37°C under 5% CO2. Three hours after the addition of MTT, the amount of formazan formed is measured spectrophotometrically at 550 nm with a Perkin Elmer HTS-7000 plate reader. The test samples are first dissolved in DMSO and then diluted with medium; the final concentration of DMSO is less than 0.25%. Normal also had the same extent of DMSO. 5-Fluorouracil (5-FU) and doxorubicin HCl are used as positive controls, and EC50 values are calculated from the mean values of data from 4 wells. (Only for Reference)